The relative importance of the cellular and humoral components of virus-specific immune responses in the pathogenesis of primary viral infections is a subject of long-standing interest. As shown in previous studies employing immunosuppressed infected mice as recipients of immune lymphoid cells or serum, some infections induce and appear to be eliminated by antiviral antibodies; cell-mediated effector functions are either unimportant or not expressed. Following infections produced by lymphocytic choriomeningitis (LCM) and vaccinia (VAC) viruses, virus elimination is associated with the preferential induction of virus-specific cytotoxic T lymphocytes (CTL) while antibody formation is either minimal or plays no essential role in host survival. It is probable that a number of virus- or host-associated factors determine whether the predominant class of response to a given infection will consist of either antibody or CTL induction. On the basis of existing evidence, we feel that a major factor is the manner in which viral antigens are first presented to the immune system, and that procedures which physically alter the association between virus and antigen-presenting cells can dictate which class predominates. The objectives of this project are: (1) to study and define the conditions under which either CTL or antibodies are induced preferentially in mice responding to VAC and LCM viruses; (2) to establish and compare, in vitro, the requirements for virus-specific secondary triggering of T cells induced during responses of each class; (3) to continue studies suggesting that cellular immunity to these viruses may be maintained, in part, by a succession of non-specific signals generated by either unrelated infectious agents or other antigens, leading to the expansion and/or differentiation of precommitted T cells. Methods to be employed include: selective depletion of T cells using antisera specific for the theta, LY-1 ion, and Ly-2,3 ion antigens, and assays of T cells for virus-specific proliferation and H-2 restricted cytotoxicity in vitro.